c-Jun can recruit JNK to phosphorylate dimerization partners via specific docking interactions

Cell. 1996 Nov 29;87(5):929-39. doi: 10.1016/s0092-8674(00)81999-6.


Structurally related serine/threonine kinases recognize similar phosphoacceptor peptides in vitro yet in vivo, they phosphorylate distinct substrates. To understand the basis for this specificity, we studied the interaction between the Jun kinases (JNKs) and Jun proteins. JNKs phosphorylate c-Jun very efficiently, JunD less efficiently, but they do not phosphorylate JunB. Effective JNK substrates require a separate docking site and specificity-conferring residues flanking the phosphoacceptor. The docking site increases the efficiency and specificity of the phosphorylation reaction. JunB has a functional JNK docking site but lacks specificity-conferring residues. Insertion of such residues brings JunB under JNK control. JunD, by contrast, lacks a JNK docking site, but its phosphoacceptor peptide is identical to that of c-Jun. Substrates such as JunD can be phosphorylated by JNK through heterodimerization with docking competent partners. Therefore, heterodimerization can affect the recognition of transcription factors by signal-regulated protein kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / physiology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Dimerization
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • Molecular Sequence Data
  • Neoplastic Stem Cells / chemistry
  • Neoplastic Stem Cells / enzymology
  • Phosphorylation
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-jun / chemistry*
  • Proto-Oncogene Proteins c-jun / physiology*
  • Substrate Specificity
  • Transcription Factors / metabolism


  • Proto-Oncogene Proteins c-jun
  • Transcription Factors
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases